Antibiotics may not be enough to stop recurrent gastric lymphoma caused by Helicobacter pylori
Research led by Dr. Anne Mueller at Stanford University School of Medicine demonstrates that successful eradication of Helicobacter may not prevent future aggressive gastric lymphoma since resting B cells are left behind. The paper by Mueller et al., "The role of antigenic drive and tumor-infiltrating accessory cells in the pathogenesis of Helicobacter-induced MALT lymphoma," appears in the September issue of The American Journal of Pathology.
Helicobacter pylori, a spiral bacterium of the stomach, infects more than half of the world’s population. It is now widely accepted that, aside from gastritis and ulcers, H. pylori is also a causative agent of gastric lymphoma, specifically gastric B cell lymphoma of mucosa-associated lymphoid tissue (MALT). While antibiotic treatment eradicates the bacteria and promotes tumor regression, the effects of re-infection on disease are more severe.
To address the effects of re-infection and the role of immune cells in disease progression, Dr. Mueller’s group used a mouse model of Helicobacter-induced MALT lymphoma that employs H. felis to mimic human disease in the mouse. Mice were infected with H. felis and maintained for 18 months before being assigned to one of three treatment groups: 1) no treatment (primarily infected), 2) antibiotic therapy to eradicate bacteria, or 3) antibiotic therapy followed by re-infection.
As expected, low-grade MALT lymphoma occurred in 35% of all infected animals. However, frank MALT lymphoma was more prevalent in re-infected animals (44%) than in primarily infected animals (25%). Transcription profiling identified B cell markers in mice that had been infected at any point in time, even after successful antibiotic treatment, suggesting that resting B cells remain in the gastric mucosa.
Lymphoid aggregates of re-infected animals also contained more proliferating cells than those of primarily infected or antibiotic-treated animals (46% vs. 23.2% or 4.8%, respectively). Closer inspection of the lymphoid aggregates revealed that the tumors were indeed derived from B cells and the main antigen-presenting cells were follicular dendritic cells. Finally, follicular dendritic cell numbers were highest in the tumors of re-infected animals followed by primarily infected and then antibiotic-treated animals, thus correlating with severity of gastric lymphoma.
Because it is the follicular dendritic cells that present antigen to T cells that in turn activate B cell proliferation, follicular dendritic cells appear to be better indicators of tumor behavior than B cells. Thus, follicular dendritic cells represent an untapped target in the fight against recurrent gastric lymphoma.
The significance of the described work is that gastric lymphoma progresses more rapidly upon secondary infection. Because resting B cells are left behind following antibiotic treatment, re-infection by H. pylori promotes the existing B cells to progress quickly into tumors. Therefore, it is important that treated patients be carefully monitored for H. pylori re-infection.
Audra Cox | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
New technique promises tunable laser devices
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...